Project Summary/Abstract Accumulating evidence suggests that diet may play an important role in the prevention of sporadic late- onset form of Alzheimer?s disease (LOAD). Our previous work from the Washington Heights, Hamilton Heights, and Inwood Columbia Aging Project (WHICAP), a longitudinal population cohort in Manhattan, has indicated that adherence to either a Mediterranean-type diet or to other healthy dietary patterns (DPs) was related to decreased risk for LOAD and better brain and cognitive measures in non-demented elderly subjects. While the underlying mechanisms for the beneficial role of these DPs are unknown, evidence based on the biological effects of individual nutrient or food components of these DPs point to inflammation. Uncontrolled chronic inflammation has been linked to increased risk of LOAD, while long-term use of anti-inflammatory treatment seems to have neuroprotective effects. We aim to elucidate the mechanism for the relationship between diet and LOAD by directly testing the hypothesis that inflammation (measured using a large number of inflammatory markers) mediates the relationship between DPs with LOAD, and LOAD-related brain and cognitive changes in WHICAP population, a well-established, multiethnic, elderly population. As an optimum combination of potent anti-inflammatory foods will be valuable candidates for interventional studies, we will also derive inflammation-explaining food combinations and test their association with both neuroimaging and clinical outcomes. Specifically, we will perform the following studies: 1) Measure an extensive panel of inflammatory biomarkers using Multiplex and develop inflammatory profiles (inflammatory marker patterns, IMP). Examine the relationship between IMPs and diet, and between IMPs and LOAD risk, or LOAD-related brain and cognitive measures. 2) Test whether the association of previous identified beneficial DPs with risk of LOAD and cognitive decline is mediated by IMPs. In a subset of the cognitively healthy participants of the study population who received brain MRI assessments, test whether previous identified association between beneficial DPs and brain measures is mediated by IMPs. 3). Empirically derive optimum inflammation- explaining dietary patterns (IDPs) that explain measured inflammatory markers? variations to the maximum. Examine the association of these IDPs with LOAD and LOAD-related brain and cognitive measures. Examine whether brain measures explain the relationship of these IDPs and cognition or LOAD. 4). Replicate and validate the findings in Aim 1 to Aim 3 in a separate cohort that has similar characteristics. Overall, successful completion of the proposed studies will provide important information on whether inflammation contributes to the association between diet and LOAD. Obtaining insight into the role of inflammation in the context of diet and LOAD may assist to prioritize public health efforts and provide a firm foundation for dietary recommendations aiming for cognitive resilience.